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02 August 2016

DNA's dynamic nature makes it well-suited to serve as the blueprint of life

Billions of years ago, when the Earth was in its infancy and biology hadn't even gotten going, the precursors to the first living organisms were probably self-replicating strands of RNA. Scientists believe that this "RNA world" provided the foundation for life as we know it

A new study could explain why DNA and not RNA, its older chemical cousin, is the main repository of genetic information. The DNA double helix is a more forgiving molecule that can contort itself into different shapes to absorb chemical damage to the basic building blocks—A, G, C and T—of genetic code. In contrast, when RNA is in the form of a double helix it is so rigid and unyielding that rather than accommodating damaged bases, it falls apart completely.

The research, published August 1, 2016 in the journal Nature Structural and Molecular Biology, underscores the dynamic nature of the DNA double helix, which is central to maintaining the stability of the genome and warding off ailments like cancer and aging. The finding will likely rewrite textbook coverage of the difference between the two purveyors of genetic information, DNA and RNA.

"There is an amazing complexity built into these simple beautiful structures, whole new layers or dimensions that we have been blinded to because we didn't have the tools to see them, until now," said Hashim M. Al-Hashimi, Ph.D., senior author of the study and professor of biochemistry at Duke University School of Medicine.

DNA's famous double helix is often depicted as a spiral staircase, with two long strands twisted around each other and steps composed of four chemical building blocks called bases. Each of these bases contain rings of carbon, along with various configurations of nitrogen, oxygen, and hydrogen. The arrangement of these atoms allow G to pair with C and A to pair with T, like interlocking gears in an elegant machine.

When Watson and Crick published their model of the DNA double helix in 1953, they predicted exactly how these pairs would fit together. Yet other researchers struggled to provide evidence of these so-called Watson-Crick base pairs. Then in 1959, a biochemist named Karst Hoogsteen took a picture of an A-T base pair that had a slightly skewed geometry, with one base rotated 180 degrees relative to the other. Since then, both Watson-Crick and Hoogsteen base pairs have been observed in still images of DNA.

Five years ago, Al-Hashimi and his team showed that base pairs constantly morph back and forth between Watson-Crick and the Hoogsteen configurations in the DNA double helix. Al-Hashimi says that Hoogsteen base pairs typically show up when DNA is bound up by a protein or damaged by chemical insults. The DNA goes back to its more straightforward pairing when it is released from the protein or has repaired the damage to its bases.

"DNA seems to use these Hoogsteen base pairs to add another dimension to its structure, morphing into different shapes to achieve added functionality inside the cell," said Al-Hashimi.

Al-Hashimi and his team wanted to know if the same phenomenon might also be occurring when RNA, the middleman between DNA and proteins, formed a double helix. Because these shifts in base pairing involve the movement of molecules at an atomic level, they are difficult to detect by conventional methods. Therefore, Al-Hashimi's graduate student Huiqing Zhou used a sophisticated imaging technique known as NMR relaxation dispersion to visualize these tiny changes. First, she designed two model double helices—one made of DNA and one made of RNA. Then, she used the NMR technique to track the flipping of individual G and A bases that make up the spiraling steps, pairing up according to Watson-Crick or Hoogsteen rules.

Prior studies indicated that at any given time, one percent of the bases in the DNA double helix were morphing into Hoogsteen base pairs. But when Zhou looked at the corresponding RNA double helix, she found absolutely no detectable movement; the base pairs were all frozen in place, stuck in the Watson-Crick configuration.

The researchers wondered if their model of RNA was an unusual exception or anomaly, so they designed a wide range of RNA molecules and tested them under a wide variety of conditions, but still none appeared to contort into the Hoogsteen configuration. They were concerned that the RNA might actually be forming Hoogsteen base pairs, but that they were happening so quickly that they weren't able to catch them in the act. Zhou added a chemical known as a methyl group to a specific spot on the bases to block Watson-Crick base pairing, so the RNA would be trapped in the Hoogsteen configuration. She was surprised to find that rather than connecting through Hoogsteen base pairs, the two strands of RNA came apart near the damage site.

"In DNA this modification is a form of damage, and it can readily be absorbed by flipping the base and forming a Hoogsteen base pair. In contrast, the same modification severely disrupts the double helical structure of RNA," said Zhou, who is lead author of the study.

The team believes that RNA doesn't form Hoogsteen base pairs because its double helical structure (known as A-form) is more compressed than DNA's (B-form) structure. As a result, RNA can't flip one base without hitting another, or without moving around atoms, which would tear apart the helix.

"For something as fundamental as the double helix, it is amazing that we are discovering these basic properties so late in the game," said Al-Hashimi. "We need to continue to zoom in to obtain a deeper understanding regarding these basic molecules of life."

Parrhesia

The two all-time most popular posts of Transudationism

A modern-day classic

All life is a form of light, and the cosmos is a holonic Holy Hologram.

Immanence ≋ Transcendence

Transudationism: mankinds' cosmic ideology.

SIC ITUR AD ASTRA!

Ascensional Transudation

Cosmic Evolution

All history is the history of the evolutionary transubstantiation of matter to Spirit via biological-life processes of Blood and Reason.

Alexandr Solzhenitsyn's concluding thoughts from his 1978 Harvard address, A World Split Apart

Alexandr Solzhenitsyn's concluding thoughts from his famous 1978 Harvard address,"A World Split Apart":

It would be retrogression to attach oneself today to the ossified formulas of the Enlightenment. Social dogmatism leaves us completely helpless in front of the trials of our times.

Even if we are spared destruction by war, our lives will have to change if we want to save life from self-destruction. We cannot avoid revising the fundamental definitions of human life and human society. Is it true that man is above everything? Is there no Superior Spirit above him? Is it right that man's life and society's activities have to be determined by material expansion in the first place? Is it permissible to promote such expansion to the detriment of our spiritual integrity?

If the world has not come to its end, it has approached a major turn in history, equal in importance to the turn from the Middle Ages to the Renaissance. It will exact from us a spiritual upsurge, we shall have to rise to a new height of vision, to a new level of life where our physical nature will not be cursed as in the Middle Ages, but, even more importantly, our spiritual being will not be trampled upon as in the Modern era.

This ascension will be similar to climbing onto the next anthropologic stage. No one on earth has any other way left but - upward.

In recent times it has been fashionable to talk of the levelling of nations, of the disappearance of different races in the melting-pot of contemporary civilization. I do not agree with this opinion, but its discussion remains another question. Here it is merely fitting to say that the disappearance of nations would have impoverished us no less than if all men had become alike, with one personality and one face. Nations are the wealth of mankind, its collective personalities; the very least of them wears its own special colours and bears within itself a special facet of divine intention.

Dr. Paul Craig Roberts

Neoconservatives used 9/11 to launch their plan for US world hegemony. Their plan fit with the interests of America’s ruling oligarchies. Wars are good for the profits of the military/security complex, about which President Eisenhower warned us in vain a half century ago. American hegemony is good for the oil industry’s control over resources and resource flows. The transformation of the Middle East into a vast American puppet state serves well the Israel Lobby’s Zionist aspirations for Israeli territorial expansion.

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MIdwest Book Review:

"The seed of the universe is the big bang, says Kyle McDermott in 'The Declaration of White Independence: The Founding Documents of Transudationism'. An explanation of this view which holds that all of current humanity and life on Earth today was intentionally set in motion all those billions of years ago, 'The Declaration of White Independence' probes matters of cosmological significance with straightforward candor and accessibility. Featuring intriguing concepts and ideas, 'The Declaration of White Independence' is highly recommended for metaphysical studies shelves."

The Music of Life: Biology Beyond Genes

and speaking of cosmic symphonies, Julianne Hough

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